Field of Invention
The present invention is related to a radiolabeled active targeting pharmaceutical composition and the use thereof, and more particularly, to a pharmaceutical composition of a bioconjugate including a biomolecule (such as a peptide and a protein) and a metal nanoparticle, and the use of the pharmaceutical composition for evaluating a thermal adjuvant therapy for tumors.
Related Art
Cancer is one of the major causes of human deaths. A conventional therapy often removes a tumor through surgery with radiotherapy and chemotherapy combined, In recent years, during the development of cancer treatment drugs, to lower the toxicity on normal tissues, targeted therapy drugs that can be precisely delivered to a treatment region, reduce the delivery times and dosage, and enhance the toxic effect on tumor tissues are under vigorous development. Biomedical materials are being developed; especially, a nanoparticle serves as a drug carrier and the passive targeting characteristic of an enhanced permeation and retention (EPR) effect is adopted to specifically accumulate drugs at a target tumor. In addition, the surface of the drug carrier is modified with a ligand with specificity, such as an antibody, a peptide or an epidermal growth factor (EGF), so that at a focus with high expression of a receptor or an antigen, active targeting increases the accumulation of drugs at a target tumor.
Many malignant tumors have the phenomenon of excessive expression of an epidermal growth factor receptor (EGFR), and the expression of an EGFR of a malignant tumor is closely associated with tumor invasiveness and therapeutic drug resistance. This type of cancer activates the EGFR to facilitate hyperplasia, angiogenesis, and metastasis and lowers apoptosis of the tumor. Therefore, the EGFR has been regarded as an important anticancer drug target in current researches.
Also, Cetuximab (Erbitux®, C225) is a human-mouse hybrid chimeric monoclonal IgG protein and has a high affinity for an EGFR, and is a therapeutic drug for tumors with high expression of an EGFR. An EGF or other ligands contend for combination with the EGFR, so as to prevent phosphorylation of a receptor and activation of relevant ferments of an EGFR to inhibit downstream signal transfer thereof, including hyperplasia, angiogenesis, metastasis, and apoptosis. Pre-clinical test show that cetuximab has obvious efficacy in inhibiting tumor growth both separately and in combination with conventional chemotherapeutic drugs, and was approved by the Food and Drug Administration in 2004, and cetuximab and irinotecan are used in combination to treat patients with metastasic colorectal cancer through expression of an EGFR.
Moreover, macromolecular carriers such as nanoparticles include organic nanoparticles such as liposomes, micelles, and dendrimers and inorganic nanoparticles such as quantum dots, iron oxide nanoparticles, and gold nanoparticles (AuNPs). Vascular endothelial tissues of a tumor have a large gap (up to hundreds of nanometers) to allow the passage of nanoparticles, which permeate from the tumor and accumulate at the tumor; and the lymphatic system of the tumor is underdeveloped, so that drugs cannot return to the circulatory system via the lymphatic system and are retained at the tumor for a long period. Such an effect is the EPR effect above. The EPR effect can be regarded as a passive targeting effect, so that drugs carried by nanoparticles reach desirable dynamic drug distribution, Also, such type of macromolecular carriers cannot penetrate healthy vascular epithelial tissues, resulting in that a very small number of chemotherapeutic drugs carried by nanometers carriers are accumulated at normal tissues. Nanomedicines have found wide application in diagnosis and therapy of cancer.
In inorganic nanoparticles, for example, as AuNPs have distinct localized surface plasma resonance and biocompatibility, various specific ligands such as peptides and proteins can be modified at the surface through the bond of a sulfur group or an amino group; AuNPs are noble metal and have low biological toxicity, so that AuNPs are currently widely used as a medium in hyperthermia therapy of tumors. However, common AuNPs only have a passive targeting effect, and actively targeted AuNPs are the trend and focus of researches in recent years.
In conclusion, so far there is still a need for a pharmaceutical composition with an active targeting capability that has both effective functions of nuclear medicine imaging diagnosis or radionuclide therapy and can effectively evaluate a therapeutic effect.